The long term goal of this proposal is to elucidate molecular mechanisms responsible for synaptic plasticity. It is well established that neurons rely on molecular recognition cues for guiding their neurites and in choosing their correct targets. While much has been learned about their recognition processes during the last few years, very little is known about the molecular details that govern the functional plasticity of synapses. Indeed, other than appreciating the importance of ion channels, intracellular messengers and kinases, we do not really understand how plasticity is orchestrated in vivo, and how activity or extracellular cues remodel synaptic arbors. This proposal aims to identify and define the molecular components required for activity-dependent structural remodeling of synapses. We hope these studies will help us outline specific molecular pathways, and begin a comprehensive dissection of synapses. We hope these studies will help us outline specific molecular pathways, and begin a comprehensive dissection of synaptic plasticity in vivo. We will focus our studies on the synapse between a Drosophila larval olfactory sensory neuron and its central target. As a first step towards a genetic screen, markers for the Drosophila larval olfactory system will be established. These markers will be used to mark selective neurons and their corresponding synaptic arborizations, and to carry out a genetic screen, markers for Drosophila larval olfactory sensory will be established.. These markers will be used to mark selective neurons and their corresponding synaptic arborizations, and to carry out a genetic screen for dominant gain-of-function and recessive loss-of-function mutations that alter specific synaptic arborization profiles. These screens will be combined with assays for activity-dependent structural changes in synaptic connections (e.g. olfactory cues). We hope this multifarious approach, bringing together genetic, molecular and physiological approaches will help elucidate basic principles of synapse biogenesis and plasticity.